The DOI matches its Crossref record; 252 of the 252 references it cites were found in a registry or an index.
Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets
Open accessAbstract
Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In addition, a significant proportion of patients with MDD do not recover baseline levels of psychosocial functioning even when they meet the conventional definition of remission (e.g. a score ≤7 on the Hamilton Depression Rating Scale (HDRS)) [2, 11, 12], suggesting that non-affective dimensions and domains are critical determinants of functional outcome.”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [11]
In the citing paper
“Only a subset of individuals with MDD (30–40 %) reach symptomatic remission after adequate treatment with a first-line antidepressant, and many patients do not reach premorbid levels of psychosocial functioning, such that a significant proportion of patients present residual symptoms.”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [11]
In the citing paper
“Several mechanisms may contribute to cognitive dysfunction in MDD, including but not limited to an over-activation of the hypothalamic–pituitary–adrenal axis, oxidative and nitrosative stress, imbalances in pathways involved in cell survival and death, and immune activation [11].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [11]
Citations
Cites
3 retracted
Gao, Y., Changquan, H., Zhao, K., Ma, L., Qiu, X., Zhang, L., Xiu, Y., Chen, L., Lü, W., Huang, C., et al. (2012) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.3845 · Cited by 165
RetractedBhattacharya, P., Pandey, A. K., Paul, S., & Patnaik, R. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.01.085 · Cited by 52
RetractedKernt, M. (2010) · Clinical ophthalmology · doi:10.2147/opth.s11216 · Cited by 34
RetractedEpigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729
Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants
Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., et al. (2003) · Science · doi:10.1126/science.1083328 · Cited by 4,321
Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., Norquist, G., Howland, R. H., Lebowitz, B., McGrath, P. J., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.1.28 · Cited by 3,879
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
The Epidemiology of Depression Across Cultures
Kessler, R. C., & Bromet, E. J. (2013) · Annual Review of Public Health · doi:10.1146/annurev-publhealth-031912-114409 · Cited by 2,657
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181
Cited by
Sorted by citations
Malhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G., et al. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415617657 · Cited by 842
“Therefore, this is an issue which is receiving increasing attention with research into both pharmacological (Carvalho et al., 2014b) and psychological strategies (Porter et al., 2014) to improve cognition.”
BackgroundCognitive remission: a novel objective for the treatment of major depression?
Bortolato, B., Miskowiak, K. W., Köhler, C. A., Maes, M., Fernandes, B. S., Berk, M., & Carvalho, A. F. (2016) · BMC Medicine · doi:10.1186/s12916-016-0560-3 · Cited by 252
Self-citationInflammatory theory of depression
Gałecki, P., & Talarowska, M. (2018) · Psychiatria Polska · doi:10.12740/pp/76863 · Cited by 192
Prefrontal cortex executive processes affected by stress in health and disease
Girotti, M., Adler, S. M., Bulin, S. E., Fucich, E. A., Paredes, D., & Morilak, D. A. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.07.004 · Cited by 176
Slyepchenko, A., Maes, M., Köhler, C. A., Anderson, G., Quevedo, J., Alves, G. S., Berk, M., Fernandes, B. S., & Carvalho, A. F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.02.002 · Cited by 89
Self-citationCognitive dysfunction in major depression: From assessment to novel therapies
Atique-Ur-Rehman, H., & Neill, J. C. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.05.013 · Cited by 72
Salagre, E., Solé, B., Tomioka, Y., Fernandes, B. S., Hidalgo-Mazzei, D., Garriga, M., Jimenez, E., Sanchez-Moreno, J., Vieta, E., & Grande, I. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.06.034 · Cited by 71
Park, M. H., Jin, H. K., & Bae, J.-S. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0399-8 · Cited by 59
Papp, M., Gruca, P., Lason-Tyburkiewicz, M., Litwa, E., Niemczyk, M., Tota-Glowczyk, K., & Willner, P. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4651-4 · Cited by 40
Alavi, N., Moghimi, E., Stephenson, C., Gutierrez, G., Jagayat, J., Kumar, A., Shao, Y., Miller, S., Yee, C. S., Stefatos, A., et al. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1113956 · Cited by 36
“The in-person and e-CBT content were intended to mirror one another and focused on: (1) an introduction to depression and the 5-part model (39), which encourage conceptualization of a specific situation or environment through an interlink of thoughts, feelings, physical reactions, and behaviours, (2) the Thought Recor…”
BackgroundMac Giollabhui, N., Alloy, L. B., Schweren, L. J. S., & Hartman, C. A. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.05.022 · Cited by 25
Metadata
- Authors
- Carvalho, A., Miskowiak, K., Hyphantis, T., Kohler, C., Alves, G., Bortolato, B., G. Sales, P., Machado-Vieira, R., Berk, M., & McIntyre, R.
- Affiliations
- Universidade Federal do Ceará (BR)
- Corresponding author
- McIntyre, Roger
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-01-22
- Volume
- 13
- Issue
- 10
- Pages
- 1819-1835
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2150071717
- Cited by
- 107
- References
- 252
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 13 · 2020: 4 · 2019: 9 · 2018: 12 · 2017: 9 · 2016: 17 · 2015: 6
- FWCI
- 10.62
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- cc-by
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- major depressive disorder, cognitive impairment, cognitive enhancement, hypothalamic-pituitary-adrenal axis, oxidative stress, nitrosative stress, neuroinflammation, inflammatory cytokines, mitochondrial dysfunction, apoptosis, neurotrophic support, minocycline, statins, N-acetylcysteine, omega-3 polyunsaturated fatty acids, erythropoietin, S-adenosylmethionine, creatine monohydrate, lithium, thiazolidinediones, glucagon-like peptide-1 analogues
- MeSH terms
- Cognition Disorders, Depression, Humans, Nootropic Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
